siRNA脱靶效应类型与规避策略

小干扰RNAs(small interfere RNAs,siRNAs)能够特异性沉默靶基因,现已广泛应用于阐明基因功能,鉴定药物靶点,开发比目前更有效的治疗药物。然而siRNA脱靶效应(off-target effects,OTEs)导致基因沉默实验中表型效应解释复杂化,引起siRNA治疗毒副作用。与siRNA有关的脱靶效应有microRNA样脱靶效应、免疫刺激、RNAi元件饱和三种类型。综述了siRNA脱靶效应类型及减轻脱靶效应的方法,以增强该技术的实用性。     

Quantitative genetics and the persistence of environmental effects in clonally propagated organisms

Abstract.— Phenotype is often viewed as a product of genes and the environment in which these genes are expressed. However, numerous studies have shown that environment can cause lasting changes in phenotype that can be passed from one generation to the next, much as genes are transmitted. In clonally propagated organisms, persistence of environmental effects has been observed in a range of plant and animal species, but has rarely been the object of study. We measured the persistence and magnitude of environmental effects on phenotype over three clonal generations in the arctic sedge Eriophorum vaginatum . We found that the environment in which tillers developed had large effects on their later performance (parental effects) and that these effects were in part independent of the size of tillers. The magnitude and persistence of environmental effects did not differ between environmental treatments or among genotypes. However, after 52 weeks of growth and two rounds of clonal propagation, grandparental treatment effects were not significant. We describe methods that can be used in quantitative genetics studies of clonal organisms to reduce bias in estimates of genotypic and environmental variance and argue that the persistence of environmental effects in clonal plant material has ecological and evolutionary consequences similar to those described for maternal environmental effects in sexual organisms.     

Distinct Subtypes of the Opioid Receptor with Allosteric Interactions in Brain Membranes

The binding isotherms of opioid receptors in rat brain membranes with [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE), [3H]dihydromorphine ([3H]DHM), and [3H]etorphine were analysed to show the effects of Mg2+, Na+, and guanine nucleotides. Four opioid receptor subtypes of delta, kappa, mu 1, and mu 2 specificities were differentiated, where necessary with the aid of specific displacing ligands. Both a guanine nucleotide [guanosine-5'-(beta, gamma-imido)triphosphate] and the cations (Na+, Mg2+) affect the affinity state of all four subtypes of the receptor. The opioid binding behaviour is found on detailed inspection to be complex, with cases of "half-of-the-sites" reactivity and of cooperativity. By their behaviour under the various ionic conditions noted, it was concluded that these subtypes are distinct, without the need to assume interconvertibility by such agents. The evidence suggests that the formation of heterologous kappa-delta or mu 1-mu 2 receptor complexes is required for stabilization of the high-affinity conformational state of the receptor. Important effects of cations in increasing the binding and regulating the equilibria of receptor association-dissociation were observed when these studies were conducted, not in the Tris-HCl buffer commonly used in opioid binding assays, but in N-tris[hydroxymethyl]-methyl-2-aminoethanesulphonate (K+) buffer (TES-KOH; 10 mM, pH 7.5): it was found that ionic species of Tris can substitute for divalent cations. Dithiothreitol effects on agonist binding in the presence and absence of the cations suggested that those cation effects involve the exchange of -SH/-SS- bonds between receptor subunits. All of the behaviour is interpreted in terms of a model involving association-dissociation equilibria of homologous and/or heterologous receptor subunits of an oligomeric opioid receptor structure.     

A new interpretation of the Stiles-Crawford effects in human vision

A retinal 3D grating chip in focal plane of the lens/pupil system of the human eye explains, via the classical crystal-optical von Laue equation, aperture-dependent phenomena in human vision (Stiles-Crawford effect I = brightness shift; Stiles-Crawford effect II = RED and BLUE shift).     

Genetic and environmental contributions to the variance of body height in a sample of first and second degree relatives.

Height was measured in a health screening of the population in Nord-Trøndelag, Norway. Correlations were computed for 24,281 pairs of spouses, 43,613 pairs of parents and offspring, 19,168 pairs of siblings, 1,318 pairs of grandparents and grandchildren, 1,218 cognate avuncular pairs, 849 noncognate avuncular pairs, 175 pairs of same-sexed twins, and smaller groups of other types of relatives. Fitting of structural equation models showed proportions of additive genetic variance of approximately 0.8 for both sexes and small sex-specific effects that probably reflect genetic dominance or environmental sibling effects. The correlations between parents and offspring were significantly lower in old than young cohorts, seeming to imply some kind of interaction effect between genes and environment. © 1992 Wiley-Liss, Inc.     

激光与细胞膜相互作用热、电效应的微观机理分析

在细胞膜电偶极矩液晶模型的基础上,用电动力学,量子统计及固体量子理论对激光与细胞膜相互作用的电学及热学效应微观机理进行研究,导出了激光-细胞膜相互作用的极化及其极化驰豫效应和温升效应公式,这些理论研究结果能解释一些相关实验。     

Man-made environmental changes affect the boundary between two taxa of Laudakia

This project tested whether, and how, man-made changes in the environment would affect the boundary between parapatric-related taxa of Laudakia ( Reptilia: Agamidae ), whose distributions meet at a boundary between ecological regions. Israel is ecologically diverse with a mesic (Mediterranean) north and an arid (Saharo-Arabian) south. The lizard hardun Laudakia stellio is represented in Israel mainly by two subspecies: the Mediterranean Lau . s . ssp. and the desert Lau. s. brachydactyla . These are conventionally distinguished by the key character, number of subdigital lamellae under the fourth toe, visible in museum specimens examined for the purpose. The results revealed that during 1935–1978, the boundary between the two subspecies had shifted 15 km southwards. This is interpreted as resulting from the documented southwards spread of irrigated agriculture. During this time, the average subdigital count of each subspecies near the inter-taxa boundary shifted slightly towards the average of the other subspecies. In each subspecies, in this area, at the same time, the coefficient of variation of the subdigital count increased. The last two processes are interpreted as reflecting reciprocal migration, enhanced by the documented expanded road system and intensified human transportation. Hence, in this case, anthropogenic developments have changed both the location and the genetic structure of the boundary between two parapatric taxa.     

Bioactive Coumarins from the Stems of Clausena emarginata

Five new coumarins, clauemarmarins I – M ( 1 – 4 ), together with 10 known analogs ( 5 – 14 ), were isolated from the stems of Clausena emarginata. Compounds 8 – 13 were obtained from this plant for the first time. Their structures were established and elucidated by comprehensive analysis of spectroscopic data. The absolute configurations of 1 – 4 were further determined by their electronic circular dichroism spectroscopy. Compounds 5 , 7 , 12 , and 14 exhibited inhibitory effects on LPS‐induced NO production. Compounds 5 – 7 showed selective neuroprotective effects in Aβ_{25 – 35} model at 10 μm .     

Effectiveness of the white halo fungus, Cephalosporium lecanii, against field populations of coffee green bug, Coccus viridis

The white halo fungus, Cephalosporium lecanii, was highly effective in the control of the coffee green bug, Coccus viridis, under field conditions. With two fortnightly applications of 16 × 10⁶ spores/ml, it caused the maximum mortality (73.1%) of the bugs 2 weeks after second application. The mortality rate was increased in the same count to 97.6% when Tween 20 (0.05%) was added to the spore suspension. Addition of starch, Lerolat N 100, Erkentrol, and Wannin to the spore suspension also increased the pathogenicity of the fungus. Among the three insecticides tested along with the fungus, 0.225% Orthene and 0.1% DDT failed to increase the mortality rate of the green bugs while 0.1% BHC hampered the effectiveness of the fungus greatly. In another trial, the fungus was applied at five different dosages and 16 × 10⁶ spores/ml was found adequate to cause a 77.9% mean mortality. The fungus was more effective as high-volume spray than as a low-volume spray. The pathogen, when tested in a drought period, was comparatively less effective, and addition of the humectant glycerol increased the mortality of the bugs due to fungus infection.     

Influence of environmental factors on daily flight activity of the filbertworm, Melissopus latiferreanus (Lepidoptera, Olethreutidae)

ABSTRACT.

• 1 Flight of Melissopus latiferreanus (Walsinghzm), the filbertworm, was influenced by a number of environmental factors including temperature, wind, and rainfall.
• 2 Few M. latiferreanus moths were trapped in light or suction traps or found in sweep nets samples when air temperatures were above 31°C or below 15°C. Moth captures were optimum when prevailing temperature was between 21 and 26°C.
• 3 Typically moth flights began at about sunset and continued throughout the night with a peak at 22.00 hours, about an hour after sunset.
• 4 Very few moths were trapped under showery and gusty conditions when wind velocity was over 16km h^?1.
• 5 More moths were captured in light traps during dark nights than on full moon nights. The pattern of captures indicated that females flew earlier than males.

     

Metabolic rates of tsetse flies in the field as measured by the excretion of injected caesium

ABSTRACT Teneral tsetse flies, Glossina morsitans morsitans Westw., were injected with labelled caesium (¹³⁷Cs) <18 h after emergence and released in the Zambezi Valley of Zimbabwe between May 1983 and June 1984, and again in February 1985. Radioactivity in flies recaptured time t days after injection indicated a three-stage exponential loss of caesium, identical for both sexes. For t≫4 the estimated rate constant (-0.119 per day) was significantly lower than for 4≫t≫12 (–0.252 per day). By day 15 about 97% of the isotope had been excreted; thereafter the loss rate fell by an order of magnitude. The data for t>4 days were well fitted by the sum of two exponentials but no smooth function was found to fit all three phases. The loss rate from the rapidly metabolized pool increased exponentially with temperature at the same rate as for male tsetse kept in the dark in the laboratory. However, the loss rate in the field was lower at every temperature, suggesting that these flies live at 2–6^oC lower than the average Stevenson screen temperature. Published estimates of hunger cycle and daily flight durations, made on the basis of measured rates of caesium excretion, are invalid because they use the assumption that flies are living in the field at screen temperatures. The data suggest that both sexes have the same metabolic rate up to the age of about 15 days, which implies that the females (being larger and having to nourish a larva in the latter stages of this period) must be less active and/or live at even lower temperatures than the males.     

Interaction between maternal effects and temperature affects diapause occurrence in the cricket Allonemobius socius

The induction of diapause can be adaptive for egg survival during unfavorable conditions, while direct development can be advantageous under favorable conditions by allowing additional generations to exploit abundant resources. Therefore, the physiological capability of a female to respond to environmental cues indicative of habitat quality by producing eggs of the appropriate developmental phenotype should be under strong selection. Additionally, developing embryos may alter the developmental trajectory initiated by the female in response to changing environmental conditions. In this study, we used a cross-fostering approach to isolate the maternal effects of parental diapause history (not previously studied) and egg-laying temperature from the influence of the incubation environment experienced by the developing embryo on the proportion of diapause eggs produced by the striped ground cricket, Allonemobius socius. We found that an interaction between egg-incubation temperature and parental diapause history strongly affected the proportion of diapause eggs produced and the proportion of eggs that hatched within a 16–18 day incubation period, while egg-laying temperature and all other interactions did not. These novel results indicate that embryos can respond directly to the environmental conditions they experience during development, but that their ability to do so is influenced by maternal effects such as parental diapause history. The results of this study not only provide evidence, for the first time, of parental diapause history affecting diapause proportions, but also raise additional questions about the mechanism by which environmental information is transmitted from parent to offspring and how offspring are able to respond to conditions experienced during their own development.     

Discussion on “Instrumental variable estimation of the causal hazard ratio,” by Linbo Wang,Eric Tchetgen Tchetgen,Torben Martinussen,Stijn Vansteelandt

Wang, et al.'s estimator for causal hazard ratios for endogenous treatments makes an important addition to a researcher's toolkit for analyzing censored duration outcomes. Their method complements existing methods in the semiparametric treatment effects literature and suggests useful avenues for future research.     

Forward from the crossroads of ecology and evolution

Community genetics is a synthesis of community ecology and evolutionary biology. It examines how genetic variation within a species affects interactions among species to change ecological community structure and diversity. The use of community genetics approaches has greatly expanded in recent years and the evidence for ecological effects of genetic diversity is growing. The goal of current community genetics research is to determine the circumstances in which, and the mechanisms by which community genetic effects occur and is the focus of the papers in this special issue. We bring a new group of researchers into the community genetics fold. Using a mixture of empirical research, literature reviews and theoretical development, we introduce novel concepts and methods that we hope will enable us to develop community genetics into the future.     

Mangroves and brackishwater pond culture in the Philippines

Around 50% of mangrove loss in the Philippines can be traced to brackishwater pond construction. The decrease in mangroves from 450 000 ha in 1920 to 132 500 ha in 1990 has been accompanied by expansion of culture ponds to 223 000 ha in 1990. The history of fishpond development in the country includes a government-sponsored fishpond boom in the 1950-g and 1960s, the proconservation decade of the 1970s followed by a shrimp fever in the 1980s. Production from brackisshwater ponds has increased from 15 900 mt worth P7.6 million in 1938 to 267 000 mt valued at P6.5 billion in 1990. On the other hand, the maximum valuation of over $11 000 ha^–1 yr^–1 for unmanaged and managed mangrove forests makes them economically on par with the most profitable pond farming systems. The loss of mangrove systems and their varied goods and services is the single most important consequence of brackishwater pond culture in the Philippines. Moreover, intensive shrimp farming is associated with other ecological and socioeconomic effects such as pollution of coastal waters and decline in domestic food crops. New legislation and enforcement of existing laws, conservation of remaining mangroves, massive rehabilitation of denuded mangrove areas, and promotion of sustainable aquaculture and fisheries are recommended.     

Temperature dependence of nitrate reductase in the psychrophilic unicellular alga Koliella antarctica and the mesophilic alga Chlorella sorokiniana

Temperature responses of nitrate reductase (NR) were studied in the psychrophilic unicellular alga, Koliella antarctica, and in the mesophilic species, Chlorella sorokiniana. Enzymes from both species were purified to near homogeneity by Blue Sepharose (Pharmacia, Uppsala, Sweden) affinity chromatography and high-resolution anion-exchange chromatography (MonoQ; Pharmacia; Uppsala, Sweden). Both enzymes have a subunit molecular mass of 100 kDa, and K. antarctica NR has a native molecular mass of 367 kDa. NR from K. antarctica used both NADPH and NADH, whereas NR from C. sorokiniana used NADH only. Both NRs used reduced methyl viologen (MVH) or benzyl viologen (BVH). In crude extracts, maximal NADH and MVH-dependent activities of cryophilic NR were found at 15 and 35 degrees C, respectively, and retained 77 and 62% of maximal activity, respectively, at 10 degrees C. Maximal NADH and MVH-dependent activities of mesophilic NR, however, were found at 25 and 45 degrees C, respectively, with only 33 and 23% of maximal activities being retained at 10 degrees C. In presence of 2 microM flavin adenine dinucleotide (FAD), activities of cryophilic NADH:NR and mesophilic NADH:NR were stable up to 25 and 35 degrees C, respectively. Arrhenius plots constructed with cryophilic and mesophilic MVH:NR rate constants, in both presence or absence of FAD, showed break points at 15 and 25 degrees C, respectively. Essentially, similar results were obtained for purified enzymes and for activities measured in crude extracts. Factors by which the rate increases by raising temperature 10 degrees C (Q10) and apparent activation energy (E(a)) values for NADH and MVH activities measured in enzyme preparations without added FAD differed slightly from those measured with FAD. Overall thermal features of the NADH and MVH activities of the cryophilic NR, including optimal temperatures, heat inactivation (with/without added FAD) and break-point temperature in Arrhenius plots, are all shifted by about 10 degrees C towards lower temperatures than those of the mesophilic enzyme. Transfer of electrons from NADH to nitrate occurs via all three redox centres within NR molecule, whereas transfer from MVH requires Mo-pterin prosthetic group only; therefore, our results strongly suggest that structural modification(s) for cold adaptation affect thermodynamic properties of each of the functional domains within NR holoenzyme in equal measure.     

Growth characteristics of low-nutrient bacteria from the north-east and central Pacific Ocean

Abstract Low-nutrient, or oligotrophic, marine bacteria, defined operationally as those which grow well in the dilute nutrient concentrations typical of natural seawaters, were found in waters of the eastern and central Pacific Ocean. All isolates tested grew in sterile unsuplemented seawater, ultraviolet-irradiated seawater, artificial seawater and charcoal-treated artificial seawater. Under optimal conditions, doubling times for low-nutrient bacteria were generally 2–5 h. Low-nutrient bacteria are heterotrophs responding to added organic substrates including glucose, proline, acetate, peptone, algal extract and yeast extract. Organic substrate concentrations ( K _s values) necessary to yield half the maximum growth rates of low-nutrient bacteria ranged from 0.8–12 μg · 1⁻¹ (0.2–4.9 μg C · 1⁻¹). Bacterial inoculum size had little effect on doubling times, whereas low oxygen tensions and low temperatures reduced growth rates. Surfaces (glass beads) increased growth rates and maximum cell densities. The results of these laboratory studies indicate that low-nutrient bacteria play a major role in marine heterotrophic transformations of dissolved organic matter.     

Lancea tibetica as the Tibetan herb: A review of its phytochemistry and pharmacology

This review, based on nearly 25 literary sources, discusses the chemical nature and biological effects of the whole plant of Lancea tibetica Hook. f. et Thoms (Scrophulariaceae). Several types of chemical constituents have been isolated from Lancea tibetica (LT) including 34 phenolpropanoids (16 lignans, 5 neolignans, 5 nonanones, 4 phenylpropanoid glycosides, and 4 propanediols), 9 flavones, 6 triterpenoids, and 11 amino acids. Various extracts and individual compounds derived from this species have been determined to possess a variety of pharmacological effects, such as anti-tumour and antioxidant functions. The results of data analysis on the chemical and pharmacological characteristics of LT support the view that this plant has many therapeutic properties, suggesting its potential as an effective herbal remedy. Finally, suggestions for further avenues of research on the chemical and pharmacological properties of LT and ways in which to further exploit LT are presented in this review.